Not applicable.
Not applicable.
The present invention relates generally to methods and devices for treating diseased blood vessels. More particularly, this invention relates to methods and devices for increasing the effective diameter of a diseased blood vessel and maintaining this effective diameter for a sufficient period of time.
Current treatments for coronary artery disease include the use of stents, angioplasty, rotational atherectomy, cutting balloons, pharmaceutical agents, and lasers. All of these treatments attempt to increase blood flow at the narrowed region of the diseased vessel by compressing the intimal (innermost) aspect of the blood vessel against the medial (layer containing smooth muscle cells) and adventitial (outermost) layers of the vessel. These treatments often fail to increase the effective diameter of the coronary artery over a long period of time.
One of the drawback of interventional or catheter-based approaches is their inability to increase the coronary artery diameter for a prolonged period of time. Restenosis, a process that occurs when the smooth muscle cells and fibroblasts are stimulated to proliferate, frequently results after these interventional procedures. This re-narrowing of the blood vessel lumen reduces the effective diameter of the artery. With stents, their ability to correct diseased blood vessels can be hampered by their failure to traverse certain lesions, the difficulty in placing them in highly tortuous vessels, and the potential immunological problems associated with leaving the stents, which are foreign substances, in the vessel. When these treatments fail to adequately correct the situation, coronary artery bypass graft surgery (CABG) is usually required. However, this surgery is often expensive and results in prolonged incapacitation and post-surgical pain for the patient.
There is thus a need for a method and device for treating diseased blood vessels that avoids the aforementioned problems associated with stents, angioplasty, or CABG surgery. Particularly desirable are methods and devices that may enable a surgeon or interventional cardiologist to treat coronary artery disease by increasing the effective diameter of the coronary artery and maintaining this effective diameter for a sufficient period of time.
The present invention avoids the aforementioned problems associated with current treatments by providing a mechanism by which the physical properties of diseased blood vessel walls can be manipulated to achieve an effective vessel lumen diameter for a prolonged period of time. The methods and devices of the present invention selectively isolate and treat the medial or adventitial layers of these diseased blood vessels. These mechanisms involve disrupting the integrity of at least one of these layers to affect the physical properties, such as vessel wall stiffness, of the diseased region.
In an exemplary embodiment, a chemical treatment is utilized to disrupt the integrity of a blood vessel wall having an atherosclerotic plaque along its wall. The chemical treatment involves delivering a digestive agent to the adventitial layer of the blood vessel at the diseased region. The quantity of digestive agent should be sufficient to degrade the collagen of the blood vessel wall and preferably promote the growth of an aneurysm at the lesion. The digestive agent may comprise a proteolytic enzyme such as highly purified mammalian collagenase. The chemical treatment of the adventitial layer can occur either before or after an angioplasty to expand the diameter of the blood vessel at the plaque. The plaque can also be isolated from the remainder of the blood vessel prior to treatment.
In another embodiment, a mechanical treatment is utilized to disrupt the integrity of a blood vessel wall having an atherosclerotic plaque along its wall. The mechanical treatment involves puncturing the blood vessel wall at the diseased region to promote the growth of an aneurysm at the lesion. As with the chemical treatment, the mechanical disruption of the vessel wall can occur either before or after an angioplasty to expand the diameter of the blood vessel at the plaque. The plaque can also be isolated from the remainder of the blood vessel prior to treatment.
Additionally, with either the chemical or mechanical treatment, growth of the aneurysm may be controlled by delivering a crosslinking agent to a medial layer of the blood vessel wall at the diseased region. The quantity of crosslinking agent should be sufficient to promote crosslinking of the collagen of the blood vessel at the lesion. The crosslinking agent may be repeatedly delivered to the vessel wall until the collagen at the lesion site is sufficiently crosslinked. Preferably, the crosslinking agent comprises glutaraldehyde, formaldehyde, carbodiimides, or diisocyanates in physiologically buffered solutions.
In yet another embodiment of the invention, chemical treatment may be utilized to disrupt the integrity of a blood vessel wall having a naturally occurring aneurysm along its wall. In this instance, the chemical treatment involves delivering a crosslinking agent to the medial layer of the blood vessel wall at the diseased region. The quantity of crosslinking agent should be sufficient to promote crosslinking of the collagen of the blood vessel at the aneurysm. The crosslinking agent may be repeatedly delivered to the vessel wall until the collagen at the aneurysm is sufficiently crosslinked. Preferably, the crosslinking agent comprises glutaraldehyde, formaldehyde, carbodiimides, or diisocyanates in physiologically buffered solutions. The aneurysm may be isolated from the remainder of the blood vessel prior to treatment.
The biological agents employed in the methods of the present invention may be delivered with a catheter, a syringe, or by topical applicators such as with a film, coating, gel or sponge. The biological agents may also be directly injected into the blood vessel wall at the diseased region. For example, the blood vessel wall may be electroporated or sonoporated prior to injecting the agents into the wall. In addition, the vessel wall could be mechanically porated prior to treatment.
In one aspect of the invention, a catheter is provided for practicing the methods of the present invention. The catheter has an elongate body for insertion into a diseased blood vessel lumen. Mounted on the elongate body is an expandable balloon having an outer wall and an inflation lumen that is in fluid communication with a source of therapeutic agent. Extending from the outer wall of the balloon is at least one microneedle. The microneedle has an injection port extending from a base of the microneedle to a distal-most end for delivering the therapeutic agent to a select layer of the blood vessel wall. The microneedle has a predetermined length sufficient to effectively puncture and extend into the select layer of the vessel wall to be treated when the balloon is filly expanded within the blood vessel lumen.
The microneedle may include a monitoring port that is in communication with a pressure sensor for detecting pressure changes between different layers of the vessel wall. The monitoring port enables the location of the distal-most end of the microneedle to be determined when it is within the blood vessel wall. The microneedle may also include a plurality of injection ports that are each capable of delivering a different therapeutic agent than the other injection ports within the microneedle. Preferably, the catheter has a plurality of microneedles arranged on the balloon and is capable of effecting delivery of the agent through a selected group of these microneedles to provide delivery in a predetermined spatial pattern.
In another aspect of the invention, the microneedle previously described can be provided on a syringe useful for practicing the methods of the present invention. The syringe can include an elongate body extending between a proximal end and a distal end. The syringe further includes a reservoir for holding the therapeutic agent. The microneedle can extend from the distal end of the elongate body. A deployment mechanism is included at the proximal end of the elongate body for effecting controlled injection of the therapeutic agent from the reservoir through the microneedle which is in fluid communication with the reservoir. The microneedle may preferably include a monitoring port that is in communication with a pressure sensor for detecting the difference in pressure inside the vessel wall and the pressure inside the vessel lumen. The monitoring port enables the location of the distal-most end of the microneedle to be determined when it is within the blood vessel wall.
In yet another aspect of this invention, a sponge is provided for practicing the methods of the present invention. The sponge has a body formed of biocompatible material loaded with a therapeutic agent for release at a later time. The therapeutic agent is effective for treating a select layer of the diseased blood vessel wall. The shape of the body may take the form of an annular ring so that the sponge can be thorascopically positioned circumferentially about the external surface of the blood vessel at the diseased region. The body may also include an adhesive layer extending about the outer surface to effect adhesion between the body and the blood vessel.
Further features of the invention, its nature and various advantages, will be more apparent from the accompanying drawings and the following detailed description of the drawings and the preferred embodiments.